Abstract: Changes in a tissue?s metabolic activity are associated with many diseases including cancer, yet there is currently no method to image these changes noninvasively, inexpensively, and at high speed. Diffuse Optical Spectroscopy (DOS) is an emerging imaging modality that is able to measure hemoglobin concentrations and calculate local blood oxygen saturation as a proxy for metabolic activity using near-infrared light. However, current DOS probes rely on manual point-by-point scanning to build up 2D images. Diffuse Optical Tomography (DOT) is a depth resolved variant of DOS, but it can take hours to generate a single image and the devices themselves are bulky and complex. There is a critical need for a low-cost, noninvasive, depth resolved, high- speed metabolic imaging modality with real-time feedback to provide frequent monitoring and assessment of diseases associated with metabolic changes such as cancer. Without such a modality, patients are subjected to more invasive procedures and unnecessary treatments with debilitating side-effects. The goal of this project is to develop a clinical instrument that produces ?ultrasound-like? images of tissue metabolism for assessing the progression of diseases that locally alter metabolism such as cancer and stroke. Using recently developed digital DOS platform that is capable of acquisition rates greater than 100 Hz, we will design and build a probe in which a single source and detector fiber are each scanned in a hypotrochoidal pattern. A hypotrochoid is a shape traced by a point on a small circle as it rolls around the inner circumference of a larger circle. When two hypocycloids are traced in parallel, the distance between the points varies over a wide range, while the center of the line connecting the two points remains stationary. These unique features enable DOS measurements to be interpreted as an axial line where each source/detector separation corresponds to a different depth below the tissue surface. This scanning pattern will enable depth-resolved measurements of tissue metabolic activity. Currently, DOS data analysis is slow, requiring several seconds to analyze a single measurement. To increase the data throughput rate, we will train an artificial neural network to predict the absorption and scattering properties of the tissue which will enable real-time analysis. Finally, we will test the new probe?s ability to monitor hemodynamic changes in breast cancer. We will use the probe to image patients undergoing neoadjuvant chemotherapy for breast cancer, and test the ability of the probe to locate and measure the hemodynamics of the tumor. It is anticipated this proposal will yield the following expected outcomes: First, a fast, low-cost prototype DOS scanner will be shown capable of providing real-time images of oxy- and deoxy-hemoglobin concentrations which are linked to tissue metabolism. Second, this device will prove capable of locating breast tumors in a diverse patient population. Third, this scanning method will enable depth resolved images of breast tumors paving the way for future work investigating chemotherapy response.